Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 76, Issue 5, Pages 989-996Publisher
SPRINGER
DOI: 10.1007/s00280-015-2880-y
Keywords
Cisplatin; Acute kidney injury; Biomarker; Lung cancer
Categories
Funding
- Ministry of Education, Science, Culture, Sports, and Technology of Japan (MEXT)
- Ministry of Health, Labour, and Welfare of Japan [08062855]
- Council for Science and Technology Policy of the Japan Society for the Promotion of Science [LS073]
- Grants-in-Aid for Scientific Research [15H04666] Funding Source: KAKEN
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Acute kidney injury (AKI) is a common and serious adverse effect of cisplatin-based chemotherapy. However, traditional markers of kidney function, such as serum creatinine, are suboptimal, because they are not sensitive measures of proximal tubular injury. We aimed to determine whether the new urinary biomarkers such as kidney injury molecule-1 (KIM-1), monocyte chemotactic protein-1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL) could detect cisplatin-induced AKI in lung cancer patients in comparison with the conventional urinary proteins such as N-acetyl-beta-d-glucosaminidase (NAG) and beta 2-microglobulin. We measured KIM-1, MCP-1, NGAL, NAG, and beta 2-microglobulin concentrations in urine samples from 11 lung cancer patients, which were collected the day before cisplatin administration and on days 3, 7, and 14. Subsequently, we evaluated these biomarkers by comparing their concentrations in 30 AKI positive (+) and 12 AKI negative (-) samples and performing receiver operating characteristic (ROC) curve analyses. The urinary levels normalized with urine creatinine of KIM-1 and MCP-1, but not NGAL, NAG, and beta 2-microglobulin in AKI (+) samples were significantly higher than those in AKI (-) samples. In addition, ROC curve analyses revealed that KIM-1 and MCP-1, but not NGAL, could detect AKI with high accuracy (area under the curve [AUC] = 0.858, 0.850, and 0.608, respectively). The combination of KIM-1 and MCP-1 outperformed either biomarker alone (AUC = 0.871). Urinary KIM-1 and MCP-1, either alone or in combination, may represent biomarkers of cisplatin-induced AKI in lung cancer patients.
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